Process for reducing aromatic nitrogen compounds



United States Patent 3,203,947 PROCESS FOR REDUCENG AROMATIC NTIROGEN COMPOUNDS William von E. Doering, New Haven, and Adnan A. R. Sayigh, North Haven, Conn, assignors to The Upjohn (Iompany, Kalamazoo, Mich, a corporation of Delaware N0 Drawing. Filed Jan. '31, 1963, Ser. No. 255,176 29 Claims. (Cl. 260-143) The present application is in part a continuation of our application Serial No. 30,756 filed May 23, 1960, now abandoned, for Reaction of Aromatic Compounds, which application in turn was a continuation-in-part of our application Serial No. 785,324 filed January 7, 1959 (now abandoned), for Reaction of Aromatic Compounds.

This invention relates to novel processes for the reduction of aromatic compounds having nitrogen in a reducible form attached directly to the aromatic ring. More particularly, it relates to the use of novel catalysts which permit the rapid reduction to the azo stage or to the hydrazo stage respectively, of aromatic nitrogen compounds in which the nitrogen is in reducible form or stage of oxidation higher than the hydrazo stage, especially azoxy and azo, whereby to improve the production thereof and increase the yields.

It is known'to employ alkaline reducing conditions to reduce aromatic compounds having nitrogen in a reducible form attached directly to the aromatic ring, such as nitro, azoxy, and azo aromatic compounds in which the nitrogen is in a higher stage of oxidation than the hydrazo stage. The usual alkaline reducing agents are alkali metal alcoholates of the lower alkanols, methanol, ethanol and the like and preferably a mixture of sodium hydroxide or potassium hydroxide and methanol. The aromatic compound such as a nitrobenzene as for instance nitrobenzene itself or nitrotoluene are reduced to the azoxy, azo and hydrazo stages by heating the compound with the alkali metal alcoholate, preferably at the normal boiling point of the mixture, as by boiling under reflux at atmospheric pressure.

The alkaline reduction as outlined above while quite useful, with certain exceptions, in reducing aromatic nitro compounds to the corresponding aromatic azoxy compounds, has not proved equally successful in further reducing the aromatic azoxy compounds generally to the azo and hydrazo stages. In the case of certain aromatic nitro compounds the yields of the corresponding aromatic azoxy compounds are low, especially in the case of the reduction of ortho-nitrotoluene to azoxytoluene. This is due to the formation of polymeric side-products. It has heretofore been necessary to use stronger reducing agents in order to reduce the aromatic nitro compound beyond the azoxy stage to the corresponding azo or hydrazo compound.

Attempts have been made to increase the yield of the aromatic azoxy compounds and to carry the reduction of such compounds further Without employing the strong reducing agents. One proposal has been to reduce the compounds with the alkali metal alcoholate under elevated temperatures and pressures. These procedures did not induce the conversion of the aromatic azoxy compounds to the corresponding aromatic hydrazo compounds, although the corresponding aromatic azo compounds could be formed. Further such procedures have proved costly and commercially undesirable.

Some success in reducing aromatic nitro compounds to the corresponding azo and hydrazo compounds under alkaline reduction conditions has been attained by the use of reduction promoters. Known reduction promoters are from a class of compounds known as naphthoquinoid compounds. Here again, however, the yield of the azoxytoluene from the orthonitrotoluene is low, as are also the yields of the aromatic hydrazo compound generally from the corresponding azoxy and azo compounds as well as the yields of the azo compounds from the azoxy compounds.

Accordingly, it is an object of the present invention to provide novel and improved catalysts for effecting the reduction of aromatic nitrogen compounds from the from azoxytoluenes and azotoluenes.

azoxy and azo stages to the hydrazo stage and of the azoxy stage to the azo stage. The improvement is very effective for the production of hydrazobenzenes from azoxybenzenes or azobenzenes including hydrazotoluenes It is very effective also for the production of azobenzenes from azoxybenzenes, including azotoluenes from azoxytoluenes. Substituent groups other than the lower alkyl groups, as

, for instance the methyl group in toluene can also be present in the azoxybenzenes and the azobenzenes and their reduction products. Such groups include the a'lk-oxy groups such as the methoxy group in the dimethoxyazoxybenzene, the dimethoxyazobenzenes and dimethoxyhydrazobenzenes; the carboxyl group as in azoxybenzoic acid; azobenzoic acid, and hydrazo'benzoic acid; the sulfonic groups as in azoxybenzene sulfonic acids, azo-benzenesulfonic acids, and hydrazobenzene sulfonic acids;

the amino groups as in azoxyanilines, azoanilines and hydrazoanilines; the halogens, fluorine, chloride bromine and iodine as in the various azoxychlorobenzenes, azochlorobenzenes and hydrazochlorobenzenes and the like with other halogens.

Another object which is to increase the yield of azoxy compounds, especially azoxytoluene from nitrobenzenes,

including orthonitrotoluenes, is the subject matter of an earlier application, Serial No. 30,756, now abandoned.

It has now been found that the alkaline reduction of reducible aromatic nitrogen compounds, i.e., nitro, azoxy and azo compounds, can be rapidly accomplished by employing as catalysts compounds selected from the group consisting of (Y0 (Tl) H OH Benzauthrone Benzanthrol Any of the compounds listed above can be used, but it is preferred to use 9-fiuorenone or 9-fluorenol since they are most efficient in giving the highest yield of reduced aromatic nitrogen compounds.

While the aryl groups of the catalysts have been shown with none of the hydrogen atoms substituted, it is possible to substitute for the hydrogen atoms a variety of groups and atoms such as alkyl groups having from 1 to 4 carbon atoms.

The catalysts of the present invention can be employed in various amounts. It is most expeditious to use from about 2% to about 5% by weight of catalyst based on weight of the reducible aromatic nitrogen compound. However, about 3.5% of the catalyst is the optimum amount. It is, of course, evident that smaller or larger amounts can 'be used.

In the practice of the present invention the reducible aromatic nitrogen compound is subjected to the reducing action of a metal alcoholate reducing agent in a reaction mixture containing at least one of the catalysts of the present invention. The term reducible aromatic nitrogen compound as used herein means that the compound is at a higher stage of oxidation than the hydrazo stage, i.e., azo, azoxy or nitro.

The following examples illustrate the invention:

Example I.-0-Nitr0toluene t0 azoxytoluene In a one-liter, four-neck, round-bottom flask, equipped with a thermometer, condenser, Trubore mechanical stirrer and addition funnel were placed 80 grams of sodium hydroxide flakes and 80 grams of methanol. The reaction flask was heated to reflux; 5 grams of '9-fluorenone were added; the temperature was 85 C.

173 grams of o-nitrotoluene (1 mole) were then added, dropwise, over a period of one hour thirty-five minutes; during the addition the temperature rose to 102 C. Heating and stirring were continued for 5 hours, at the end of which time steam distillation removed 9-fluorenone, o-toluidine and unreacted o-nitrotoluene, if any. The temperature of the reaction mixture was not allowed to rise above 110 C.; this was accomplished by occasional addition of water.

The reaction mixture was cooled to 80 C. and extracted with 300 ml. of benzene, which was filtered in case insoluble tar was present.

The benzene was evaporated on a steam bath by blowing with inert gas or it was distilled in vacuo. An oil was obtained which crystallized immediately on cooling to room temperature, weighing 105.7 grams (corresponding to 90% of theory); its infra red spectrum was identical with that of azoxytoluene.

Example II.Az0xybenzene to hydrazobenzene In a one-liter, three-neck, round-bottom flask, equipped with a Trubore mechanical stirrer, condenser, and thermometer were placed the above quantities of material and the mixture was heated to reflux while agitating for 46 hours; the temperature was 96-98 C.

At the end of the reaction time the reaction mixture became tan in color. 500 mls. of water were added dropwise to dissolve sodium formate and to precipitate the hydrazobenzene which was filtered with suction, washed thoroughly with about 1.5 liters of water and dried thoroughly. The product weighed 130 grams, amounting to a quantitative yield, melting at -123 C. (reported melting point C.).

Its infrared spectrum was identical with hydrazobenzene indiacted by NH absorption at 2.9 microns and the disappearance of the N=N absorption at 10.6 microns in azoxybenzene.

Example III.-Az0xytoluene to hydrazotolluene Grams Azoxytoluene Sodium hydroxide 108 Methanol 192 9-fluorenone 5 In a one-liter, three-neck, round-bottom flask, equipped with a Trubore stirrer, condenser, and thermometer were placed the above quantities of material and the mixture was heated to reflux while agitating for 46 hours; the temperature was 9698 C. At the end of the reaction time, the reaction mixture became tan in color. After addition of 400 ml. of methanol, the mixture was cooled to room temperature and filtered. The solid was washed thoroughly with water to free the solid hydrazotoluene from sodium formate and alkali. After drying, the solid hydrazotoluene weighed 110 grams, amounting to 83% of theory. Its infrared spectrum showed it to be identical with hydrazotoluene. In addition to hydrazotoluene, a mixture of azoxytoluene and azotoluene was also isolated.

Example IV.High temperature and pressure reduction of azoxybenzene to hydrazobenzene A one-liter iron pressure vessel was charged with 210 grams of azoxybenzene, 288 grams of methanol, grams of flaked caustic soda, and 10 grams of crude fluorenone (purity 60-70% and closed and sealed. The vessel was placed in an oil heating bath and warmed rapidly to 115 C., with agitation; a pressure build-up of 15-18 pounds occurred. The temperature was permitted to use very slowly to 1l8-122 C., at which point reaction started as evidenced by an exotherm and rapid increase of pressure to 45-55 pounds. The reaction was controlled by limiting the oil temperature to 126 C., until reaction had subsided. Heating was continued for five hours by proper manipulation of the oil bath temperature to give a steady internal temperature of 124- 125 C. The pressure slowly dropped to 35-45 pounds.

The reaction mixture was cooled to 90 C., the residual pressure was bled oil through a condenser, and 300 ml. of cold water were added to drown the batch. The vessel was opened and discharged into 500 mls. of hot water. The organic hydrazobenzene precipitate was removed by filtration and Washed with 90 C. water. The light tan cake of hydrazobenzene (250 grams wet) was discharged, and converted in the usual manner to benzidine dihydrochloride.

The yield of benzidine is usually 70-75% (from azoxy) and the material balance is from 9095%.

Equally good results have been obtained using benzanthrone, anthrone, benzophenone, and xanthrone as the ketone catalyst in the reduction, and their corresponding carbinols.

Example V In place of the 5 grams of the 9-fluorenone set forth in Examples 1, 3.5 grams of benzanthrone are used.

The reduction is otherwise carried out in the same mannor as set forth in Example I. The yield of azoxytoluone obtained was 90%.

Example VI In place of the 5 grams of 9-fluorenone employed in Example I, 5 grams of anthrone are used; the conditions of the reduction being the same as set forth in Example I. Here a yield of 84% of azoxytoluene is obtained.

Example VII In place of the 5 grams of 9-fluorenone set forth in Example I, 5 grams of benzophenone are employed, the conditions of reduction otherwise being the same. Here 78% of azoxytoluene is obtained.

Example VIII In place of the 5 grams of 9-fiuorenone set forth in Example I, 5 grams of xanthrone are employed, the conditions of the reduction being otherwise the same. Here 76% of azoxytoluene is obtained.

Likewise, in Examples V to VIII instead of the ketones mentioned, the corresponding carbinols may be substituted. In such cases, the amount of carbinol used is equivalent to that of the ketone, and the procedure is exactly the same as that indicated in the preceding examples. The yields obtained are identical to those given above as will be exemplified in the following example.

Example 1X In a one-liter, three-neck, round-bottom flask, equipped with condenser, thermometer, and Trubore mechanical stirrer, were placed azoxybenzene (140 g., 0.7 m.), sodium hydroxide (108 g.), methanol (192 g.) and 9- fluorenol (5 g.); the mixture was heated to reflux while agitating for 46 hours; the temperature was 96-98. At the end of the reaction time the reaction mixture became tan in color and 500 ml. of Water were added dropwise to dissolve sodium formate and to precipitate the hydrazobenzene which was filtered with suction, washed thoroughly with about 1.5 liter of Water and dried thoroughly. The solid, after crystallization from ethanol, Weighed 130 g., amounting to a qualitative yield, MP. 126128 (reported 131, 127, 124). its infrared spectrum showed it to be identical with an authentic sample of hydrazobenzene.

It is also possible as will be shown in the following example to use mixtures of the catalysts of the instant invention and obtain equally excellent results.

Example X This experiment was the same as Example IX except that in place of the 5 g. of 9-fluorenol, a mixture of 2.5 g. of fluorenol and 2.5 g. of fluorenone were used. The results obtained were the same as above.

I It is to be understood that mixtures of catalysts also refer to mixture of ketones and mixtures of carbinols as well as mixtures of ketones and carbinols.

Example XI.Nilr0benzene to hydrazobenzene Grams Ortho-nitrobenzene 371.6 Sodium hydroxide 270 Methanol 360 9-fluorenone 12 red spectroscopy. The product was found to be mainly azoxybenzene.

The reaction mixture was then heated for an additional reaction period of 2 hours, at a temperature of to 96 C. Infrared analysis of a sample at this stage showed the product to be a mixture of azoxybenzene, 40 percent, and azobenzene 60 percent.

To this reaction mixture was then charged an additional 90 grams of flaked sodium hydroxide, grams of methanol and 4 grams of 9-fluorenone, and the heating continued under reflux at a temperature of about 90 to 96 C. for an additional period of 12 hours. Thereupon the reaction mixture was cooled and the product worked up in the usual manner. There was obtained 272.7 grams of hydrazobenzene melting at 126 C.

Example XII A run was made similar to that described in Example XI except that ortho-nitrotoluene was used as starting material. The initial product as determined by infrared analysis was azoxytoluene which upon further heating as in Example XI was converted to a mixture of azoxytoluene and azotoluene.

Upon charging additional sodium hydroxide, methanol and 9-fluorenone and continuing the reaction period, there was obtained a product which was hydrazotoluene, in good yield.

The novel catalysts of the present invention permit the reduction of the various reducible aromatic nitrogen compounds to various stages by varying the amounts of sodium hydroxide and methanol as well as the particular type and amount of the catalyst. As illustrated in the examples set forth above, it is possible to reduce the aromatic nitrogen compound to the hydrazo derivative directly or merely to reduce it to the azoxy or azo derivative.

A study of the examples will show that the catalysts may be added to the reaction mixture in various ways and at various times. The reducible aromatic nitrogen compound, the metal alcoholate reducing agent and the catalyst may all be mixed together, and then the mixture can be heated to reflux, or the catalyst may be added to the metal alcoholate and this mixture heated to reflux, at which time the reducible aromatic nitrogen compound is added to the refluxing mixture. It is preferred to add the catalyst to the sodium hydroxide and methanol and to heat this mixture to reflux, at which time the reducible aromatic nitrogen compound is added to the mixture.

It is also possible, by the use of these catalysts, to reduce substituted derivatives of the aromatic nitrogen compounds to the corresponding substituted reduced aromatic compounds.

Without limiting ourselves thereby, we believe that the effectiveness of the compounds of the present invention is due to the formation of a rapid ketone-carbinol oxidationreduction system. Thus, it has been proposed that the formation of azoxybenzene in the reduction of nitrobenzene results from condensation between the intermediates phenyl hydroxylamine and nitrosobenzene; this has been confirmed and it has been found that a rapid equilibrium between phenyl hydroxylamines and nitrosobenzene exists. In the methanolic sodium hydroxide reduction of o-nitroluene an extensive oxidation of the methyl group could take place. The addition of a catalytic amount of a ketone, therefore, appears to decrease the extent of this side reaction by increasing both the rate of the formation of nitrosotoluene and its subsequent reduction to o-tolyl hydroxylamine which in turn condenses with the nitroso compound to give azoxytoluene; in this the ketone acts as a hydrogen transfer agent. Similarly, in the catalyzed methanolic sodium hydroxide reduction of azoxy to azo and also of azoxy and azo compounds to their hydrazo derivatives, 9-fluorenone has presumably acted as an intermediary in the reaction. The role of the catalyst must, therefore, involve the initial reduction of fluorenone to fluorenol by the reducing medium, resulting in the formation of the rapid oxidation-reduction system fiuorenone-fiuorenol, which is essential in effecting further reduction of the azo and azoxy compounds to their hydrazo derivatives. The equilibration of the fluorenonefluorenol system in alkali apparently involves a hydride transfer:

wherein X is a divalent radical selected from the class consisting of N=il N=N, and NH-NH and Y is selected from the group consisting of hydrogen, alkyl, alkoxy, carboxy,

sulfonic, amino and halo, by reduction, using an alkali metal alcoholate solution as the reducing agent, of a correspondingly substituted compound selected from the class consisting of wherein Y isas hereinbefore defined and X is selected from group consisting of and N=N-- provided that X in the starting material is in a lower state of oxidation than X in the end product the improvement which comprises carrying out the reduction in the presence of a catalytic amount of a hydrogen transfer agent having an oxidised form and a reduced form which provides in the reduction mixture a ketone-carbinol oxidation-reduction system, said hydrogen transfer agent in its oxidised form being a member of the group consisting of benzophenone, 9-fluorenone, anthrone, xanthone, and benzanthrone and in its reduced form a member of the group consisting of benzhydrol, 9-fiuorenol, hydranthranol, xanthhydrol and benzanthrol,

2. In a process for making a hydrazobenzene compound by reduction of the corresponding nitrobenzene compound using an alkali metal alcoholate solution as the reducing agent the improvement which comprises carrying out the reduction in the presence of a catalytic amount of a hydrogen transfer agent having an oxidised form and a reduced form which provides in the reduction mixture 2. ketone-carbinol oxidation-reduction system, said hydrogen transfer agent in its oxidised form being a member of the group consisting of benzophenone, 9-fluorenone, anthrone, xanthone, and benzanthrone and in its reduced form a member of the group consisting of benzhydrol, 9- fluorenol, hydranthranol, xanthhydrol and benzanthrol, and continuing the reduction until the production of the hydrazobenzene compound is substantially complete.

3. The process of claim 2 wherein the nitrobenzene compound is nitrobenzene itself.

4. The process of claim 2 wherein the nitrobenzene is O-nit-robenzene.

5. In a process for making a hydrazobenzene compound by reduction of the corresponding azoxybenzene compound using an alkali metal alcoholate solution as reducing agent, the improvement which comprises carrying out the reduction in the presence of a catalytic amount of a hydrogen transfer agent having an oxidised form and a reduced form which provides in the reduction mixture a ketone-carbinol oxidation-reduction system, said hydrogen transfer agent in its oxidised form being a member of the group consisting of benzophenone, 9-fluorenone, anthrone, xanthone, and benzanthrone and in its reduced form a member of the group consisting of benzhydrol, 9- fluorenol, hydranthranol, xanthhydrol and benzanthrol, and continuing the reduction until the production of the hydrazobenzene compound is substantially complete.

6. The process of claim 5 in which the azoxybenzene compound is azoxybenzene itself.

7. The process of claim 5 in which the azoxybenzene compound is o,o-dimethylazoxybenzene.

8. In a process for making a hydrazobenzene compound by reduction of the corresponding azobenzene compound using an alkali metal alcoholate solution as a reducing agent, the improvement which comprises carrying out the reduction in the presence of a catalytic amount of a hydrogen transfer agent having an oxidised form and a reduced form which provides in the reduction mixture a ketonecarbinol oxidation-reduction system, said hydrogen transfer agent in its oxidised form being a member of the group consisting of benzophenone, 9-fluorenone, anthrone, xanthone, and benzanthrone and in its reduced form a member of the group consisting of benzhydrol, 9-fluorenol, hydranthranol, xanthhydrol and benzanthrol.

9. The process of claim 8 wherein the azobenzene compound is azobenzene itself.

10. The process of claim 8 wherein the azobenzene compound is o,o'-dimethy1azobenzene.

11. In a process for making an azobenzene compound by reduction of the corresponding azoxybenzene compound using an alkali metal alcoholate solution as reducing agent the improvement which comprises carrying out the reduction in the presence of a catalytic amount of a hydrogen transfer agent having an oxidised form and a reduced form which provides in the reduction mixture a ketone-carbinol oxidation-reduction system, said hydrogen transfer agent in its oxidised form being a member of the group consisting of benzophenone, 9- fluorenone, anthrone, xanthone, and benzanthrone and in its reduced form a member of the group consisting of benzhydrol, 9-fluorenol, hydranthranol, xanthhydrol and benzanthrol.

12. In a process for making an azoxybenzene compound by reduction with an alkali metal alcoholate solution of 2 nitro benzene compound the improvement wherein the reduction is carried out at a reaction temperature of about 96 to C. in the presence of a catalytic amount of a hydrogen transfer agent having an oxidized form and a reduced form which provides in the reduction mixture a ketone-carbinol oxidation-reduction system, said hydrogen transfer agent in its oxidized form being a member of the group consisting of benzophenone, 9- fluorenone, anthrone, xanthone and benzanthrone and in its reduced form a member of the group consisting of benzhydrol, 9-fluorenol, hydranthranol, xanthhydrol and benzanthrol.

13. A process according to claim 12 in which the nitrobenzene compound is ortho-nitrotoluene.

14. The process as set forth in claim 12 wherein from about 2 percent to about 5 percent by weight of the hydrogen transfer agent based on the Weight of the nitrobenzene compound is added to the reaction mixture.

15. The process of claim 12 wherein the hydrogen transfer agent in its oxidized form is 9-fluorenone and in its reduced form is 9-fluorenol.

16. The process of claim 12 wherein the hydrogen transfer agent in its oxidized form is benzophenone and in its reduced form is benzohydrol.

17. The process of claim 12 wherein the hydrogen transfer agent in its oxidized form is benzanthrone and in its reduced form is benzanthrol.

18. The process of claim 12 wherein the hydrogen transfer agent in its oxidized form is anthrone and in its reduced form is hydranthranol.

19. The process of claim 12 wherein the hydrogen 10 transfer agent in its oxidized form is Xanthone and in its reduced form is xanthydrol.

20. The process according to claim 12 in which the nitrobenzene compound is nitrobenzene.

No references cited.

CHARLES B. PARKER, Primary Examiner. IRVING MARCUS, Examiner. 

1. IN A PROCESS FOR THE PREPARATION OF A COMPOUND HAVING THE FORMULA 